A 45-year-old black male presented with a chief complaint of worsening “discomfort” under the prosthesis which was fitted for his right eye. He explained he had acquired the prosthesis 30 years ago secondary to a childhood accident. His medical history was noncontributory and he reported no allergies of any kind.
|For 30 years, he’s worn a prosthetic. Now, the socket of this 45-year-old patient’s enucleated eye has been causing him such significant discomfort he sought medical help. How can his history combined with this presentation lead you to the root of his pain?|
Best-corrected visual acuity through +0.50DS spectacles measured 20/20 OS. The pertinent external clinical data OD is demonstrated in the photograph. The lesion was not suppurative. The extraocular muscle motilities, confrontation visual fields and anterior segment findings were normal OS. His intraocular pressure measured 16mm Hg OS. A dilated fundus examination of his left eye revealed normal nerves and quiet peripheries.
Given the patient’s history of recent onset irritation questioning about potential chemical exposure to the area or prosthesis was completed. The region was tested with litmus paper for evidence of substance exposure. The region was examined for pseudomembranes and mucopurulent discharge. The lymph nodes under the chin and in the neck were also examined.
The diagnosis in this case is toxic/allergic exposure of the palpebral conjunctiva of the enucleated eye, O.D.
Toxic conjunctivitis, sometimes referred to as chemical keratitis or toxic follicular conjunctivitis, is an entity that results when the cornea, palpebral and bulbar conjunctiva are exposed to any number or combinations of foreign substances.1-4 The process may occur unilaterally or bilaterally. Symptoms occurring from chronic exposure include ocular itching, burning and tearing, corneal punctate epitheliopathy, injection of the bulbar and palpebral conjunctivae, chemosis of the conjunctiva and adnexa, along with inferior and or superior conjunctival follicles and papillae in the absence of lymphadenopathy.1-4 If the reaction is substantial, involving a large area or the exposure is diffuse, an anterior chamber reaction is possible. The severity of the external damage and internal inflammation depends upon the nature of the offending substance (caustic, bland, acid, base, solid, liquid, gas, light) along with the duration (long time vs. short time) and type of contact (direct or indirect).5 It is important to recall that phototoxicity (exposure to ultraviolet light, typically from a welders arc or sunlight reflected by snow) is a keratitis-producing source.4,6 When exposure to an agent or combination of substances or irritants (mechanical included) continues without treatment or antidote, a fibrovascular adaptation of the conjunctival tissue may ensue.7 This finding is known as pannus.7
Typically, patients present in one of two ways. Either they report to the office with an unexplained red eye, oblivious to a causative vector or they report explaining that their eye was accidentally exposed to something noxious. In the case of the phenomenon known as medicamentosa, there will be a history of starting a new ocular medication, preparation (i.e., contact lens solution, rewetting drop) or contact lens.8 Diagnosis is typically straight forward. The keratitis is termed punctuate epitheliopathy and exactly resembles its description (diffuse, dot-like compromise either confined to the area of contact or distributed equally to the entire tissue). The conjunctivae, while injected, will appear elevated, boggy and chemotic without being firm, warm or painful to the touch. In some instances, the term “watch glass” is employed because the domed appearance of the conjunctiva, as it is juxtaposed against the cornea, resembles the way a watch’s crystal interfaces with its casing. Likewise the skin and adnexa have the potential to be involved with a response ranging from itching to full-blown uticaria or boggy edema.
The toxic/allergic response is classically considered to be an over-reaction of the body’s immune system to materials known as immunogens or allergens.7-13 The reaction can be innate or acquired. This overaction is manifested when the body responds hyperactively to any exogenous material. The chemical may be overtly destructive (gasoline, ammonia, chlorine) or may be a topical medicine, a contact lens, contact lens solution, dust or dander.1-13 The resultant tissue response results from the release of cytokines and chemoattractants. When researchers analyzed the tissue response which produces pannus following chemical injury they found the tissue to contain epithelial hyperplasia in 62% of the cases, active fibrosis in 66% of the cases, severe inflammation in 21% of the cases, giant cell reaction in 28% of the cases and stromal calcification in 14% of cases.7 Further, goblet cell absence was associated with squamous metaplasia of the conjunctiva and associated with long- duration-of-insult indicating that chemical injuries may produce lasting effects even after the event has passed.7
The immune system has two divisions each containing several components. The cellular immune system has a cellular component (leukocytes and other supportive cells) and a humoral component (antibodies).13 The system relies primarily on the cellular system to recognize foreign substances and initiate the first attack.13,14 The components of the cellular system include granulocytes (neutrophils, basophils, eosinophils) and macrophages (phagocytize antigen and present it to T cells). It also includes T helper lymphocytes which recognize foreign proteins presented by macrophages and bind to them causing the release of lymphokines, alerting other lymphocytes to the presence of foreign antigens and cytotoxic T cells which destroy abnormal host cells. Suppressor T cells also play a role by suppressing the immune response. B cells differentiate into plasma cells producing antibodies against foreign invaders. An antibody is a complex glycoprotein produced by plasma cells that are highly specific for the antigen that stimulated their production. Mast cells are also included as members of the cellular immune team.13,14
Not withstanding the other players on team, the key component to the ocular allergic response is the mast cell. When mast cells interact with specific allergens, like a lock being opened by a key, they open (degranulation) discharging chemical substances called mediators into the surrounding tissues.11 The primary chemical mediators include histamine (responsible for increased vascular permeability, vasodilatation, bronchial constriction and increased secretion of mucous), neutral proteases (generate other inflammatory mediators) and arachidonic acid (crucial component of the cyclooxygenase pathway leading to production of prostaglandins and leukotrienes).15
Pathophysiologically, there are four types of hypersensitivity reactions.13 Type I reactions are immediate hypersensitivity reactions or anaphylactic reactions. These reactions produce sudden mass degranulation of mast cells mediated by the antibody IgE.13 Type II reactions are classified as autoimmune and involve an impaired ability of the body ability to distinguish self from non-self.13 Abnormalities in this element of the system give rise to disease where auto-antibodies are produced and directed against the host.13 Type III reactions involve combined formations of antigen and antibody known as immune complexes.13 Offending triggers may be intrinsic (i.e. a protein molecule) or extrinsic (a penicillin molecule) producing a significant tissue response.13 Type IV reactions, sometimes referred to as cell mediated hypersensitivity reactions, involve the T lymphocytes and lymphokines.13 The reaction is classically delayed until a sufficient volume of antigens stimulate the chemical cascade.13 Here, the individual has the potential to respond when the appropriate levels of antigen become present. This may take one exposure or one hundred exposures. Classically, following the response (which is rarely life-threatening), the patient is bewildered, recognizing they had been engaged with that substance a number of times without any complication whatsoever. The Type I and IV reactions govern toxic/allergic keratoconjunctival disease.
In the ocular tissues, the result of these chemical exchanges are seen in the form of conjunctival and adnexal vasodilation producing chemosis and edema.12,14 Conjunctival follicles are hyperplasia of lymphoid tissue within the eyelid stroma and papillae are hyperplastic palpebral conjunctival epithelium infiltrated by lymphocytes and plasma cells.13,15
Since there are many strata of ocular allergic reactions, management is primarily aimed at eliminating the causative substance and reducing symptomatology.1-17 In the event of an acute injury, lavage should be completed with single and double lid eversion. If patients call on the telephone to report that they have been involved in an accidental chemical exposure, they should be advised to copiously lavage immediately before coming to the office. Patients who require over-the-phone first aide should be advised to brush off all powdered chemicals before attempting lavage it and to make sure the recommended antidote for the exposure is irrigation. This information should be on the product label or material safety data sheet (MSDS). The procedure for self-lavage is to run water from a tap or nozzle into cupped hands, placing the eye into the formed receptacle. Copious blinking enables the rinse.5,16 In the office, irrigation can be augmented manually by using a sterile ophthalmic saline applied forcefully and directly to all surfaces or by flushing the eye with a sterile intravenous saline solution run through a Morgan lensTM apparatus.5,16
Following any necessary first aide, cold compress, artificial teardrops and ointments can soothe and lubricate the conjunctiva, skin and cornea, on an as needed basis. Topical decongestants produce vasconstriction, reducing hyperemia, chemosis and other symptoms by retarding the release of the chemical mediators into the tissues from the blood stream. Topical antihistamines along with antihistamine/mast cell stabilizing combinations and oral antihistamines are also excellent therapies for acute signs and symptoms.15 Non-steroidal anti-inflammatory drugs (NSAIDS) may offer significant pain relief in moderate cases with topical steroidal preparations reserved for the most severe presentations.1-15 In some instances, where the cornea is sufficiently tattered, topical antibiotic coverage may be prudent. Bandage contact lenses and cycloplegia can also be included on an as necessary basis.17 Finally, oral analgesics such as aspirin or ibuprofen can be used to settle excessive discomfort and any referred pain.17 If corneal edema is significant topical hypertonic drops and ointments can be used QD to QID to restore normal levels of hydration.
Given no specific chemical identification, the prosthesis and exposed orbital conjunctiva were cleaned with copious lavage. The case was then handled like any other case of conjunctivitis: Use of the prosthesis was temporarily discontinued, an antibiotic steroid combination ointment was prescribed TID along with good hygiene. The presumed toxic conjunctivitis resolved without complication over the course of seven days.
1. Balali-Mood M, Hefazi M. Comparison of early and late toxic effects of sulfur mustard in Iranian veterans. Basic Clin Pharmacol Toxicol. 2006;99(4):273-82.
2. Wirbelauer C. Management of the red eye for the primary care physician. Am J Med. 2006;119(4):302-6.
3. Lubeck D, Greene JS. Corneal injuries. Emerg Med Clin North Am. 1988;6(1):73-94.
4. Records RE. Primary care of ocular emergencies. 2. Thermal, chemical, and nontraumatic eye injuries. Postgrad Med. 1979;65(5):157-60, 163.
5. Burns FR, Paterson CA. Prompt irrigation of chemical eye injuries may avert severe damage. Occup Health Saf. 1989;58(4):33-6.
6. Peate WF. Work-related eye injuries and illnesses. Am Fam Physician. 2007;75(7):1017-22.
7. Fatima A, Iftekhar G, Sangwan VS et al. Ocular surface changes in limbal stem cell deficiency caused by chemical injury: a histologic study of excised pannus from recipients of cultured corneal epithelium. Eye. 2007;21(6): E publication ahead of print, advance on-line publication: www.nature.com/eye/journal/vaop/ncurrent/index.html#08062007.
8. Baudouin C, Pisella PJ, Fillacier K et al. Ocular surface inflammatory changes induced by topical antiglaucoma drugs: human and animal studies. Ophthalmology. 1999 Mar;106(3):556-63.
9. Baudouin C. Allergic reaction to topical eyedrops. Curr Opin Allergy Clin Immunol. 2005;5(5):459-63.
10. Jackson WB. Differentiating Conjunctivitis of Diverse Origins. Surv of Ophthalmol. 1993;37(4)suppl:91-104.
11. Butrus S, Portela R. Ocular allergy: diagnosis and treatment. Ophthalmol Clin North Am. 2005;18(4):485-92.
12. Jennings B. Mechanisms, Diagnosis and Management of Common Ocular Allergies. J Am Opt Ass. 1990;61(6)suppl:s33-s41.
13. Onofrey BE. Principles of Immunology and The Immune Response. In: Onofrey, BE, Ed. Clinical Optometric Pharmacology and Therapeutics. Philadelphia, PA; JB Lippincott Co 1994 :(68):1-13.
14. Leonardi A. Emerging drugs for ocular allergy. Expert Opin Emerg Drugs. 2005;10(3):505-20.
15. Schultz BL. Pharmacology of ocular allergy. Curr Opin Allergy Clin Immunol. 2006;6(5):383-9.
16. Ikeda N, Hayasaka S, Hayasaka Y et al. Alkali burns of the eye: effect of immediate copious irrigation with tap water on their severity. Ophthalmologica. 2006;220(4):225-
17. Wilson SA, Last A. Management of corneal abrasions. Am Fam Physician. 2004;70(1):123-8.